MRAs show varied efficacy in heart failure across ejection fractions

A meta-analysis of almost 14,000 patients with heart failure (HF) assessed the differential impact of mineralocorticoid receptor antagonists (MRAs) on patients with HF across the spectrum of ejection fractions. The conclusion was that although the evidence was somewhat stronger for patients with reduced ejection fractions, the non-steroidal MRA finerenone also showed efficacy in patients with higher ejection fractions.

While MRAs are well-established in reducing hospitalisations and mortality in HF with reduced ejection fraction (HFrEF), their benefits in HF with mildly reduced (HFmrEF) or preserved ejection fraction (HFpEF) have been less clear. Prof. Pardeep Jhund (University of Glasgow, Scotland) presented a meta-analysis on this topic, which was simultaneously published in The Lancet. The analysis pooled data from 4 major trials: RALES and EMPHASIS-HF, which focused on HFrEF, and TOPCAT and FINEARTS-HF, which focused on HFmrEF and HFpEF [1–5].

The meta-analysis included 13,846 patients and revealed that MRAs significantly reduced the risk of cardiovascular death or HF hospitalisation versus placebo, with a hazard ratio (HR) of 0.77 (95% CI 0.72–0.83; P<0.001). However, the efficacy varied significantly between the HF subtypes. In patients with HFrEF, MRAs showed greater benefit, reducing the risk by 34% (HR 0.66; 95% CI 0.59–0.73; P<0.001). In contrast, the reduction was more modest in patients with HFmrEF or HFpEF, with a 13% risk reduction (HR 0.87; 95% CI 0.79–0.95; P=0.004).

The analysis also found that MRAs significantly decreased HF hospitalisations as an individual component in both HFrEF (HR 0.63; 95% CI 0.55–0.72; P<0.001) and HFmrEF/HFpEF (HR 0.82; 95% CI 0.74–0.91; P<0.001) populations. Cardiovascular death was reduced in patients with HFrEF (HR 0.72; 95% CI 0.63–0.82; P<0.001) but not in those with HFmrEF or HFpEF (HR 0.92; 95% CI 0.80–1.05; P=0.20). Similarly, all-cause mortality was reduced in HFrEF (HR 0.73; 95% CI 0.65–0.83; P<0.001) but not in patients with HFmrEF or HFpEF (HR 0.94; 95% CI 0.85–1.03; P=0.19).

In terms of safety, the use of MRAs was associated with a doubled risk of hyperkalaemia compared with placebo (OR 2.27; 95% CI 2.02–2.56; P<0.001), though the incidence of severe hyperkalaemia (serum potassium >6.0 mmol/L) remained low at 2.9% versus 1.4%, and there were no deaths due to hyperkalaemia. In line with this, MRAs reduced the risk of hypokalaemia by half (OR 0.51; 95% CI 0.45–0.57; P<0.001).

These findings suggest that MRAs reduce cardiovascular death and hospitalisations across the spectrum of EF. It remains to be investigated whether differences between newer generations of non-steroidal MRAs that have differential effects in cardiac and kidney tissue and different tolerability than traditional steroidal MRAs explain positive findings in FINEARTS-HF relative to other trials. This new meta-analysis reinforces the need for tailored treatment approaches depending on the type of HF and ejection fraction at the individual level.

Relevant readings:

• FINEARTS-HF: Finerenone improves outcomes in heart failure with preserved ejection fraction (ESC 2024)
• Application of guideline-directed medical therapy in patients with HFrEF in the Netherlands (HFA 2024)
• Antagonising the mineralocorticoid receptor beneficial for patients with diabetes and CKD (ESC 2021)
• Finerenone reduces the risk of AF onset in patients with CKD and diabetes (ACC 2021)

 

1. 
   
   1. Jhund P, et al. MRAs in heart failure – An individual patient data meta-analysis of randomised trials. HOTLINE 7, ESC Congress 2024, 30 Aug–02 Sept, London, UK.
   2. Jhund P, et al. Lancet 2024;404(10458):1119-1131.
   3. Pitt B, et al. N Engl J Med 1999;341(10):709-17.
   4. Zannad F, et al. N Engl J Med 2011;364(1):11-21.
   5. Pitt B, et al. N Engl J Med 2014;370(15):1383-92.
   6. Solommn S, et al. N Engl J Med 2024;391:1475-1485.

Copyright ©2024 Medicom Medical Publishers



Posted on 7 November 20247 November 2024